Breast cancer is an extremely complicated disease. But at its simplest, it can be divided into two types: estrogen receptor (ER) positive breast cancer, which accounts for about 70% of all breast cancers, and ER negative breast cancer. Endocrine therapies, sometimes called hormonal therapies, target the estrogen receptor positive cancer. Thus, in the past, ER has been used as a biomarker to determining whether to treat breast cancer with endocrine therapy or some other non-endocrine based therapy.
Recently it has been shown that in breast cancers, the androgen receptor (AR) is more widely expressed than estrogen receptor (ER) alpha or progesterone receptor (PR). Accordingly, AR has recently emerged as a useful marker for the further refinement of breast cancer subtype classification (1, 2). It has been found that in one particular study involving 2171 invasive breast cancers of women enrolled in the Nurses' Health Study, 77% were positive for AR by immunohistochemistry (IHC) (3). Among the subtypes, 88% of ER+ (i.e., estrogen receptor positive), 59% of HER2+, and 32% of triple negative breast cancers (ER−/PR−/HER2−) were positive for AR expression by IHC (3). Similar to ER and PR, AR expression is associated with a well-differentiated state (4) and more indolent breast cancers (5).
Since ER+ tumors are stimulated by estrogen, therapies such as the ER antagonist tamoxifen or aromatase inhibitors (AIs), which block the conversion of androgens to estrogens, are generally effective for inhibiting the progression of such tumors. However, 30-50% of all ER+ breast cancer patients display de novo resistance to these traditional endocrine therapies and ultimately all metastatic ER+ breast cancers acquire resistance (6, 7).
Interestingly, even among ER+ tumors, some breast cancers respond well to a traditional endocrine therapy while others do not. Currently, there is no reliable method for determining whether a breast cancer will respond better to a traditional endocrine therapy or an anti-androgen therapy. Thus, in most cases, the first line of chemotherapy treatment for breast cancer uses a traditional endocrine therapy, which is effective in only some of the breast cancer patients. As with most chemotherapy treatments, administering a traditional endocrine therapy to those who are not likely to respond positively causes undue physical and financial stress and burden.
Accordingly, there is a need for a method for determining whether a particular breast cancer will respond positively to an endocrine therapy.